What Is The Potential Impact Of Shear Stress-induced Endothelial Cell Mechanotransduction On The Regulation Of Krüppel-like Factor 2 (KLF2) Expression In The Context Of Atherosclerotic Plaque Development In ApoE-/- Mice With Pre-existing Hypertension?

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The potential impact of shear stress-induced endothelial cell mechanotransduction on KLF2 expression in hypertensive ApoE-/- mice is significant in the context of atherosclerotic plaque development. Here's a structured summary:

  1. Atherosclerosis and Model: ApoE-/- mice are prone to atherosclerosis due to hyperlipidemia. Hypertension exacerbates this by altering vascular mechanics.

  2. Shear Stress and Mechanotransduction: Shear stress, the force of blood flow on endothelial cells, activates mechanotransduction pathways (e.g., PECAM-1, VEGFR) leading to signaling cascades (PI3K/Akt, ERK, NF-κB) that regulate gene expression, including KLF2.

  3. KLF2 Role: KLF2 is atheroprotective, promoting anti-inflammatory responses, nitric oxide production, and endothelial health. It is induced by laminar shear stress.

  4. Hypertension Effects: Hypertension disrupts normal shear stress, causing disturbed flow patterns. This leads to reduced KLF2 expression, impairing endothelial function and increasing atherosclerosis susceptibility.

  5. Pathological Consequences: Lower KLF2 levels result in increased inflammation, oxidative stress, and endothelial dysfunction. This promotes lipid uptake, foam cell formation, and plaque instability.

  6. Regional Variations: Areas with disturbed flow (e.g., arterial branches) may have reduced KLF2, exacerbating plaque formation. Straight regions might retain higher KLF2 but are overwhelmed by systemic hypertension effects.

  7. Conclusion: In hypertensive ApoE-/- mice, altered shear stress reduces KLF2 expression, promoting atherosclerotic plaque development through increased inflammation and endothelial dysfunction.

Thus, shear stress-induced mechanotransduction plays a crucial role in regulating KLF2, which is disrupted in hypertension, accelerating atherosclerosis.